Lidocaine is a widely used anesthetic and antiarrhythmic agent. One of its major metabolites in man is the mono- N-deethylated product MEGX. Preliminary evidence was recently presented that N-hydroxylidocaine and N-hydroxyMEGX are also major metabolites in man. Because of the carcinogenic propensity of other N-hydroxyamides, we have synthesized the potential N-hydroxyamide metabolites and tested for their formation in normal subjects using chemical ionization mass spectrometry and stable isotope labeling. We have also determined the mutagenic potential of the metabolites using the Ames' test and the carcinogeic potential in mice. Results of these experiments indicate that the N-hydroxyamides are not major metabolites of lidocaine in man and that they are neither mutagenic nor carcinogenic based on the testing procedures described. We are now attempting to determine whether these metabolites are formed in patients receiving the drug.